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鉴定百日咳博德特氏菌的一种新保护性抗原。

Identification of a new protective antigen of Bordetella pertussis.

机构信息

Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.

出版信息

Vaccine. 2011 Nov 3;29(47):8731-9. doi: 10.1016/j.vaccine.2011.07.143. Epub 2011 Aug 30.

Abstract

Antigenic proteins whose expression is induced under iron starvation, an environmental condition that bacterial pathogens have to face during colonization, might be potential candidates for improved vaccine. By mean of immune proteomics we identified novel antigens of Bordetella pertussis maximally expressed under iron limitation. Among them, Bp1152 (named as IRP1-3) showed a particularly strong reaction with human IgG purified from pooled sera of pertussis-infected individuals. Computer analysis showed IRP1-3 as a dimeric membrane protein potentially involved in iron uptake. Experimental data revealed the surface-exposure of this protein and showed its increase under iron starvation to be independent of bacterial virulence phase. Immunization of mice with the recombinant IRP1-3 resulted in a strong antibody response. These antibodies not only recognized the native protein on bacterial surface but also promote effective bacterial phagocytosis by human PMN, a key protecting activity against this pathogen. Accordingly, IRP1-3 proved protective against B. pertussis infection in mouse model. Expression of IRP1-3 was found conserved among clinical isolates of B. pertussis and positively regulated by iron starvation in these strains. Taken together these results suggest that this protein might be an interesting novel vaccine candidate.

摘要

在铁饥饿条件下表达的抗原蛋白是细菌病原体在定植过程中必须面对的一种环境条件,可能是改良疫苗的潜在候选物。通过免疫蛋白质组学,我们鉴定了博德特氏菌在铁限制下最大表达的新型抗原。其中,Bp1152(命名为 IRP1-3)与人感染百日咳个体的混合血清中纯化的 IgG 反应特别强烈。计算机分析表明,IRP1-3 是一种二聚体膜蛋白,可能参与铁的摄取。实验数据显示该蛋白暴露于表面,并且其在铁饥饿下的增加与细菌毒力阶段无关。用重组 IRP1-3 免疫小鼠可引起强烈的抗体反应。这些抗体不仅识别细菌表面的天然蛋白,还可促进人 PMN 有效吞噬细菌,这是针对该病原体的关键保护活性。因此,IRP1-3 在小鼠模型中被证明对博德特氏菌感染具有保护作用。在博德特氏菌的临床分离株中发现了 IRP1-3 的表达保守性,并且在这些菌株中,铁饥饿对其表达进行了正向调节。这些结果表明,该蛋白可能是一种有趣的新型疫苗候选物。

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